抑制肺泡巨噬细胞对全氟异丁烯致急性肺损伤的影响

The effect of alveolar macrophage inhibition in perfluoroisobutylene-induced acute lung injury

目的初步探讨肺泡巨噬细胞(AM)在全氟异丁烯(PFIB)急性吸入性肺损伤中的作用。方法248只雄性KM小鼠,随机分为对照、氯化钆(GdC l3)、PFIB和GdC l3/PFIB 4组。其中PFIB与GdC l3/PFIB组行全身暴露动态吸入PFIB染毒(染毒剂量为130 mg/m3×5 m in),对照与GdC l3组行过滤空气暴露;GdC l3与GdC l3/PFIB组在染毒前48 h及24 h各静脉注射(iv)1次GdC l3(10μg/g)以抑制AM功能,对照与PFIB组iv等剂量生理氯化钠。分别在染毒结束后8、12、24、48和72 h,测定支气管肺泡灌洗液(BALF)中总蛋白含量及肺湿/干重比;染毒后24 h行组织及超微病理检查;并观察在190 mg/m3×5 m in染毒剂量下小鼠7 d内的死亡率。结果预先抑制AM功能可显著降低PFIB染毒小鼠死亡率,改善PFIB所致的肺组织及超微病理改变;在染毒后8、12和24 h,可显著降低BALF中总蛋白含量,明显降低肺湿/干重比。结论AM在介导PFIB所致急性肺损伤过程中发挥了重要作用,其内在机制有待进一步探讨。

Objective To investigate preliminarily the role of alveolar macrophage （AM） in perfluoroisobutylene （PFIB）- induced acute lung injury. Methods 248 male KM mice were randomly divided into four groups （ namely control group, GdCl3 group, PFIB group and GdCl3/PFIB group）, among which the PFIB and GdCl3/PFIB groups were exposed to PFIB at the concentration of 130 mg/m^3 for 5 minutes in a flow-past whole-body chamber, while the control and GdCl3 groups were exposed to the filtered air in a similar manner. Before PFIB or filtered air exposure, the GdCl3 and GdCl3/PFIB groups were pretreated with GdCl3 intravenously （ 10μg/g） at 48 hours and 24 hours, respectively, and the control and PFIB groups were injected the same dose of normal saline at the corresponding time-points. The content of total protein in brochoalveolar lavage fluid （BALF） and the lung wet-to-dry weight ratio was determined at 8, 12, 24, 48 and 72 hours post PFIB exposure, with histopathological and ultrastructural examination being done at 24 hours and the mortality rate induced by PFIB exposure at 190 mg/m^3 for 5 minutes within the 7-day observation period being recorded. Results When AM inhibition was achieved by GdCl3 pretreatment, death of mice induced by an over-LCt50 concentration of PFIB （ at 190 mg/m^3 for 5minutes） dropped dramatically, which was well supported by the amelioration in histopathological and ultrastructural changes observed at 24 hours post PFIB exposure as well as significant declination in content of BALF total protein and lung wet-to-dry weight ratio observed at 8, 12 and 24 hours post exposure, respectively in the GdCl3/PFIB group. Conclusion AM plays an important role in the pathogenesis of PFIB-induced acute lung injury, the underlying mechanism of which needs to be further clarified.